Predicting bowel function after diverting stoma closure in patients with rectal cancer.

Background: Patients with rectal cancer undergoing laparoscopic anterior resection and diverting stomas often suffer from bowel dysfunction after stoma closure, impairing their quality of life. This study aims to develop a machine learning tool to predict bowel function after diverting stoma closure. Methods: Clinicopathological data and post-operative follow-up information from patients with mid-low rectal cancer after diverting stoma closure were collected and analyzed. Patients were randomly divided into training and test sets in a 7:3 ratio. A machine learning model was developed in the training set to predict major low anterior resection syndrome (LARS) and evaluated in the test set. Decision curve analysis (DCA) was used to assess clinical utility. Results: The study included 396 eligible patients who underwent laparoscopic anterior resection and diverting stoma in Tongji Hospital affiliated with Huazhong University of Science and Technology from 1 January 2012 to 31 December 2020. The interval between stoma creation and closure, neoadjuvant therapy, and body mass index were identified as the three most crucial characteristics associated with patients experiencing major LARS in our cohort. The machine learning model achieved an area under the receiver operating characteristic curve (AUC) of 0.78 [95% confidence interval (CI): 0.74-0.83] in the training set (n=277) and 0.74 (95% CI: 0.70-0.79) in the test set (n=119), and area under the precision-recall curve (AUPRC) of 0.73 and 0.69, respectively, with sensitivity of 0.67 and specificity of 0.66 for the test set. DCA confirmed clinical applicability. Conclusions: This study developed a machine learning model to predict major LARS in rectal cancer patients after diverting stoma closure, aiding their decision-making and counseling.

Golgi dispersal in cancer stem cells promotes chemoresistance of colorectal cancer via the Golgi stress response.

Chemotherapy is a crucial treatment for colorectal tumors. However, its efficacy is restricted by chemoresistance. Recently, Golgi dispersal has been suggested to be a potential response to chemotherapy, particularly to drugs that induce DNA damage. However, the underlying mechanisms by which Golgi dispersal enhances the capacity to resist DNA-damaging agents remain unclear. Here, we demonstrated that DNA-damaging agents triggered Golgi dispersal in colorectal cancer (CRC), and cancer stem cells (CSCs) possessed a greater degree of Golgi dispersal compared with differentiated cancer cells (non-CSCs). We further revealed that Golgi dispersal conferred resistance against the lethal effects of DNA-damaging agents. Momentously, Golgi dispersal activated the Golgi stress response via the PKCα/GSK3α/TFE3 axis, resulting in enhanced protein and vesicle trafficking, which facilitated drug efflux through ABCG2. Identification of Golgi dispersal indicated an unexpected pathway regulating chemoresistance in CRC.

The silent information regulator 1 agonist SRT1720 reduces experimental intracerebral hemorrhagic brain injury by regulating the blood-brain barrier integrity.

Intracerebral hemorrhage (ICH) is a significant public health matter that has no effective treatment. ICH-induced destruction of the blood-brain barrier (BBB) leads to neurological deterioration. Astrocytic sonic hedgehog (SHH) alleviates brain injury by maintaining the integrity of the BBB after ICH. Silent information regulator 1 (SIRT1) is neuroprotective in several central nervous system diseases via BBB regulation. It is also a possible influential factor of the SHH signaling pathway. Nevertheless, the role of SIRT1 on BBB and the underlying pathological process associated with the SHH signaling pathway after ICH remain unclear. We established an intracerebral hemorrhagic mouse model by collagenase injection. SRT1720 (a selective agonist of SIRT1) was used to evaluate the effect of SIRT1 on BBB integrity after ICH. SIRT1 expression was reduced in the mouse brain after ICH. SRT1720 attenuated neurobehavioral impairments and brain edema of ICH mouse. After ICH induction, SRT1720 improved BBB integrity and tight junction expressions in the mouse brain. The SHH signaling pathway-related factors smoothened and glioma-associated oncogene homolog-1 were increased with the intervention of SRT1720, while cyclopamine (a specific inhibitor of the SHH signaling pathway) reversed these effects. These findings suggest that SIRT1 protects from ICH by altering BBB permeability and tight junction expression levels. This process is associated with the SHH signaling pathway, suggesting that SIRT1 may be a potential therapeutic target for ICH.

Nuclear Softness Promotes the Metastatic Potential of Large-Nucleated Colorectal Cancer Cells via the ErbB4-Akt1-Lamin A/C Signaling Pathway.

Abnormal nuclear enlargement is a diagnostic and physical hallmark of malignant tumors. Large nuclei are positively associated with an increased risk of developing metastasis; however, a large nucleus is inevitably more resistant to cell migration due to its size. The present study demonstrated that the nuclear size of primary colorectal cancer (CRC) cells at an advanced stage was larger than cells at an early stage. In addition, the nuclei of CRC liver metastases were larger than those of the corresponding primary CRC tissues. CRC cells were sorted into large-nucleated cells (LNCs) and small-nucleated cells (SNCs). Purified LNCs exhibited greater constricted migratory and metastatic capacity than SNCs in vitro and in vivo. Mechanistically, ErbB4 was highly expressed in LNCs, which phosphorylated lamin A/C at serine 22 via the ErbB4-Akt1 signaling pathway. Furthermore, the level of phosphorylated lamin A/C was a negative determinant of nuclear stiffness. Taken together, CRC LNCs possessed greater constricted migratory and metastatic potential than SNCs due to ErbB4-Akt1-mediated lamin A/C phosphorylation and nuclear softening. These results may provide a potential treatment strategy for tumor metastasis by targeting nuclear stiffness in patients with cancer, particularly CRC.

Identification and validation of molecular subtypes and prognostic signature for stage I and stage II gastric cancer based on neutrophil extracellular traps.

Purpose: This study identified subtypes and prognostic signature of stage I and stage II gastric cancer based on neutrophil extracellular trap (NET)-related genes. Methods: The gene expression data associated with stage I and stage II gastric cancer were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. NET-related genes were obtained from previous reference. Differentially expressed NET-related genes were selected by consensus cluster analysis. The differences in immune infiltration between two subtypes were analyzed. Prognosis-related genes were further screened by univariate Cox regression analysis. Gene Set Enrichment Analysis (GSEA) of prognostic signatures was conducted with clusterprofiler. Finally, a miRNA-mRNA-transcription factor (TF) network was constructed. Results: Total 43 differential NET-related genes were obtained and two subtypes were obtained based on these genes. Patients of cluster 2 had a better prognosis compared to cluster 1. Eight types of immune cells were differential in infiltration level between two subtypes. Following univariate Cox regression analysis, two genes of CXC chemokine receptor 4 (CXCR4) and nuclear factor, erythroid 2-like 2 (NFE2L2) significantly related to patient survival were selected. GSEA of single gene revealed that CXCR4 was associated with allograft rejection and NFE2L2 was associated with drug metabolism-cytochrome P450. A network with 421 miRNA-mRNA-TF regulatory pairs was constructed. Conclusion: The present study identified two subtypes and a prognostic signature for stage I and stage II gastric cancer based on NET-related genes.

Comparisons of drug-eluting balloon versus drug-eluting stent for the treatment of cancer patients presenting with acute myocardial infarction.

BACKGROUND: Treatment for cancer patients presenting with acute myocardial infarction (AMI) remains challenging. The objective of the study was to investigate the safety and efficiency of drug eluting balloon (DEB) versus drug eluting stent (DES) in this high-risk group. METHODS: Between 1st January 2017 and 1st January 2022, cancer patients admitted to Beijing Chaoyang Hospital with AMI were retrospectively enrolled. The primary endpoint was major adverse cardiovascular event (MACE). The secondary endpoints included major bleeding events, heart failure and cardiac complications. RESULTS: A total of 164 cancer patients presenting with AMI were included in the final analysis. Patients treated with DEB had a numerically lower rate of MACE than those treated with DES during a median follow-up of 21.8 months (22.9% vs. 37.1%, p = 0.23). Patients treated with DEB had a trend towards lower rate of major bleeding events than patients treated with DES (6.3% vs. 18.1%, HR 2.96, 95% CI [0.88, 9.92], p = 0.08). There were no significant differences between the two groups with regards to the rate of heart failure (4.2% vs. 9.5%, p = 0.32) and cardiac complications (0.0% vs. 2.6%, p = 0.56). CONCLUSIONS: The present study demonstrated that in cancer patients with AMI, DEB had a trend towards lower rate of major bleeding events and a numerically lower rate of MACE compared with DES.

Comparing Long-Term survival benefits of hepatocellular carcinoma between thermal ablation monotherapy and combined therapy with transarterial Chemoembolization: A propensity score matched study.

PURPOSE: To compare the long-term survival benefits of hepatocellular carcinoma (HCC) in thermal ablation (TA) monotherapy and TA combined with transarterial chemoembolization (TACE) using propensity score matching (PSM). MATERIALS AND METHODS: Between 1 January 2015 and 28 February 2021, 432 consecutive patients (357 men, 75 women; age range, 20-87 years) with HCC (Barcelona Clinic Liver Cancer stage 0-B) underwent ultrasonography-guided percutaneous TA, which included radiofrequency ablation (n = 340) and microwave ablation (n = 92). The association between combined treatment of TACE prior to TA versus TA monotherapy and survival prognosis was evaluated, including (a) local tumor progression (LTP) by using a logistic regression model, and (b) disease-free survival (DFS) and (c) overall survival (OS) by using a Cox proportional hazards model according to propensity score matched data. RESULTS: After PSM, the final matched cohort consisted of 146 patients, with 73 receiving TA monotherapy and 73 receiving TA combined with TACE. The cumulative LTP rates did not show a significant difference between the two groups (P = 0.960). Neither the DFS nor OS rate was significantly different between the two groups (P = 0.070 and P = 0.680, respectively). The multivariate analysis identified two significant findings. Firstly, ultrasound echo, minimal ablative margin, and high risk of tumor burden score were found to be associated with LTP. Secondly, the type of TA, Child-Turcotte-Pugh grade, ablation time, and lymphocyte-monocyte ratio were identified as independent prognostic factors for OS. CONCLUSION: The differences in LTP, DFS, and OS rates of HCC patients were found to be statistically non-significant between TA monotherapy and TACE + TA groups. For HCC patients with BCLC stage 0-B, the combination treatment of TACE prior to TA may be not associated with long-term survival benefits relative to TA monotherapy.

Growth differentiation factor 15 predicts cardiovascular events in stable coronary artery disease.

BACKGROUND: Growth differentiation factor 15 (GDF-15) has been explored as a potential biomarker for various inflammatory diseases and cardiovascular events. This study aimed to assess the predictive role of GDF-15 levels in cardiovascular events and all-cause mortality, considering traditional risk factors and other biomarkers. METHODS: A prospective study was conducted and 3699 patients with stable coronary artery disease (CAD) were enrolled into the research. Baseline GDF-15 levels were measured. Median follow-up was 3.1 years during the study. We analyzed clinical variables and several biomarkers. Multivariable Cox regression analysis was performed to evaluate prognostic performance of GDF-15 levels in predicting myocardial infarction (MI), heart failure, stroke, cardiovascular death, and non-cardiovascular death. RESULTS: Baseline GDF-15 levels for 3699 patients were grouped by quartile (≤ 1153, 1153-1888, 1888-3043, > 3043 ng/L). Higher GDF-15 levels were associated with older age, male gender, history of hypertension, and elevated levels of N-terminal pro B-type natriuretic peptide (NT-pro BNP), soluble suppression of tumorigenesis-2 (sST2), and creatine (each with P < 0.001). Adjusting for established risk factors and biomarkers in Cox proportional hazards models, a 1 standard deviation (SD) increase in GDF-15 was associated with elevated risk of clinical events [hazard ratio (HR) = 2.18, 95% confidence interval (CI): (1.52-3.11)], including: MI [HR = 2.83 95% CI: (1.03-7.74)], heart failure [HR = 2.71 95% CI: (1.18-6.23)], cardiovascular and non-cardiovascular death [HR = 2.48, 95% CI (1.49-4.11)] during the median follow up of 3.1 years. CONCLUSIONS: Higher levels of GDF-15 consistently provides prognostic information for cardiovascular events and all cause death, independent of clinical risk factors and other biomarkers. GDF-15 could be considered as a valuable addition to future risk prediction model in secondary prevention for predicting clinical events in patient with stable CAD.

Machine learning model for prediction of low anterior resection syndrome following laparoscopic anterior resection of rectal cancer: A multicenter study.

BACKGROUND: Low anterior resection syndrome (LARS) severely impairs patient postoperative quality of life, especially major LARS. However, there are few tools that can accurately predict major LARS in clinical practice. AIM: To develop a machine learning model using preoperative and intraoperative factors for predicting major LARS following laparoscopic surgery of rectal cancer in Chinese populations. METHODS: Clinical data and follow-up information of patients who received laparoscopic anterior resection for rectal cancer from two medical centers (one discovery cohort and one external validation cohort) were included in this retrospective study. For the discovery cohort, the machine learning prediction algorithms were developed and internally validated. In the external validation cohort, we evaluated the trained model using various performance metrics. Further, the clinical utility of the model was tested by decision curve analysis. RESULTS: Overall, 1651 patients were included in the present study. Anastomotic height, neoadjuvant therapy, diverting stoma, body mass index, clinical stage, specimen length, tumor size, and age were the risk factors associated with major LARS. They were used to construct the machine learning model to predict major LARS. The trained random forest (RF) model performed with an area under the curve of 0.852 and a sensitivity of 0.795 (95%CI: 0.681-0.877), a specificity of 0.758 (95%CI: 0.671-0.828), and Brier score of 0.166 in the external validation set. Compared to the previous preoperative LARS score model, the current model exhibited superior predictive performance in predicting major LARS in our cohort (accuracy of 0.772 for the RF model vs 0.355 for the preoperative LARS score model). CONCLUSION: We developed and validated a robust tool for predicting major LARS. This model could potentially be used in the clinic to identify patients with a high risk of developing major LARS and then improve the quality of life.

Comparisons of different new-generation transcatheter aortic valve implantation devices for patients with severe aortic stenosis: a systematic review and network meta-analysis.

BACKGROUND: Whether there are differences among the new-generation transcatheter aortic valve implantation (TAVI) devices for patients with aortic stenosis remains unclear. The aim of the study was to compare the efficiency and safety of different new-generation TAVI devices for patients with aortic stenosis. MATERIALS AND METHODS: A comprehensive search of PubMed, Embase and Web of Science from their inception to 1 February 2022. Randomized clinical trials and observational studies that compared two or more different TAVI devices were enroled. Pairwise meta-analysis and frequentist network meta-analysis were conducted to pool the outcome estimates of interest. RESULTS: A total of 79 studies were finally included. According to the surface under the cumulative ranking, the top two ranked valves for lower rates of events were as follows: direct flow medical (DFM) (4.6%) and Lotus (48.8%) for lower rate of device success; Sapien 3 (16.8%) and DFM (19.7%) for lower mortality; DFM (8.6%) and Sapien 3 (25.5%) for lower rates of stroke; Evolut (27.6%) and DFM (35.8%) for lower rates of major and life-threatening bleeding; Portico (22.6%) and Sapien 3 (41.9%) for lower rates of acute kidney injury; Acurate (8.6%) and DFM (13.2%) for lower rates of permanent pacemaker implantation; Lotus (0.3%) and Sapien 3 (22.7%) for lower rates of paravalvular leak; Evolut (1.4%) and Portico (29.1%) for lower rates of mean aortic valve gradients. CONCLUSIONS: The findings of the present study suggested that the device success rates were comparable among these new-generation valves except for DFM. After excluding DFM, Sapien 3 might be the best effective for decreased mortality and stroke; Lotus might be the best effective for decreased paravalvular leak; Evolut might be the best effective for decreased major and life-threatening bleeding and mean aortic valve gradients; Acurate and Portico might be the best effective for decreased permanent pacemaker implantation and acute kidney injury, respectively.

Artificial intelligence assists surgeons' decision-making of temporary ileostomy in patients with rectal cancer who have received anterior resection.

BACKGROUND: Due to the difficult evaluation of the risk of anastomotic leakage (AL) after rectal cancer resection, the decision to perform a temporary ileostomy is not easily distinguishable. The aim of the present study was to develop an artificial intelligence (AI) model for identifying the risk of AL to assist surgeons in the selective implementation of a temporary ileostomy. MATERIALS AND METHODS: The data from 2240 patients with rectal cancer who received anterior resection were collected, and these patients were divided into one training and two test cohorts. Five AI algorithms, such as support vector machine (SVM), logistic regression (LR), Naive Bayes (NB), stochastic gradient descent (SGD) and random forest (RF) were employed to develop predictive models using clinical variables and were assessed using the two test cohorts. RESULTS: The SVM model indicated good discernment of AL, and might have increased the implementation of temporary ileostomy in patients with AL in the training cohort (p < 0.001). Following the assessment of the two test cohorts, the SVM model could identify AL in a favorable manner, which performed with positive predictive values of 0.150 (0.091-0.234) and 0.151 (0.091-0.237), and negative predictive values of 0.977 (0.958-0.988) and 0.986 (0.969-0.994), respectively. It is important to note that the implementation of temporary ileostomy in patients without AL would have been significantly reduced (p < 0.001) and which would have been significantly increased in patients with AL (p < 0.05). CONCLUSION: The model (https://alrisk.21cloudbox.com/) indicated good discernment of AL, which may be used to assist the surgeon's decision-making of performing temporary ileostomy.

Bacterial Growth-Induced Tobramycin Smart Release Self-Healing Hydrogel for Pseudomonas aeruginosa-Infected Burn Wound Healing.

Burns are a common health problem worldwide and are highly susceptible to bacterial infections that are difficult to handle with ordinary wound dressings. Therefore, burn wound repair is extremely challenging in clinical practice. Herein, a series of self-healing hydrogels (QCS/OD/TOB/PPY@PDA) with good electrical conductivity and antioxidant activity were prepared on the basis of quaternized chitosan (QCS), oxidized dextran (OD), tobramycin (TOB), and polydopamine-coated polypyrrole nanowires (PPY@PDA NWs). These Schiff base cross-links between the aminoglycoside antibiotic TOB and OD enable TOB to be slowly released and responsive to pH. Interestingly, the acidic substances during the bacteria growth process can induce the on-demand release of TOB, avoiding the abuse of antibiotics. The antibacterial results showed that the QCS/OD/TOB/PPY@PDA9 hydrogel could kill high concentrations of Pseudomonas aeruginosa (PA), Staphylococcus aureus, and Escherichia coli in a short time and showed a bactericidal effect for up to 11 days in an agar plate diffusion experiment, while showing good in vivo antibacterial activity. Excellent and long-lasting antibacterial properties make it suitable for severely infected wounds. Furthermore, the incorporation of PPY@PDA endowed the hydrogel with near-infrared (NIR) irradiation assisted bactericidal activity of drug-resistant bacteria, conductivity, and antioxidant activity. Most importantly, in the PA-infected burn wound model, the QCS/OD/TOB/PPY@PDA9 hydrogel more effectively controlled wound inflammation levels and promoted collagen deposition, vascular generation, and earlier wound closure compared to Tegaderm dressings. Therefore, the TOB smart release hydrogels with on-demand delivery are extremely advantageous for bacterial-infected burn wound healing.

Facile preparation of melamine foam with superhydrophobic performance and its system integration with prototype equipment for the clean-up of oil spills on water surface.

A simple and efficient method was developed to rectify the surface properties of commercial melamine foam. The process was based on the siloxane coating originated from the silanization of methyltrimethoxysilane and tetraethoxysilane. The foam can be easily scaled up by employing low-cost chemicals and devices. The studies on the properties of the material showed that the wettability of melamine foam was changed to superhydrophobic with a water contact angle of 156° due to the presence of alkylsilane. The modified foam exhibited excellent oil/water selectivity and high oil absorption capacities of 77-163 times its own weight. The retention of absorption capacity was greater than 97% after 5000 cycles compression. These fascinating characteristics made the modified foam exceptional recyclability for commonly organic solvents and oils without obvious dissolution/swelling. Based on these inspiring results, the material can be employed for the continuous separation of various oil compounds floating on water surface with the assistance of a vacuum pump. Moreover, the prepared material was integrated with an apparatus to develop a prototype oil collector for the remediation of oil spills in a larger open-air environment. The devices could be readily used in a range of real-world applications, including industrial oil spill clean-up.

Fração de Ejeção do Ventrículo Esquerdo Aumentada, Diminuída ou Estável ao Longo do Tempo em uma Série de 626 Pacientes com Insuficiência Cardíaca que Receberam Tratamento Médico / Increased, Decreased, or Stable Left Ventricle Ejection Fraction over Time in a Series of 626 Heart Failure Patients Receiving Medical Treatment

Resumo Fundamento: A fração de ejeção (FE) tem sido utilizada em análises fenotípicas e na tomada de decisões sobre o tratamento de insuficiência cardíaca (IC). Assim, a FE tornou-se parte fundamental da prática clínica diária. Objetivo: Este estudo tem como objetivo investigar características, preditores e desfechos associados a alterações da FE em pacientes com diferentes tipos de IC grave. Métodos: Foram incluídos neste estudo 626 pacientes com IC grave e classe III-IV da New York Heart Association (NYHA). Os pacientes foram classificados em três grupos de acordo com as alterações da FE, ou seja, FE aumentada (FE-A), definida como aumento da FE ≥10%, FE diminuída (FE-D), definida como diminuição da FE ≥10%, e FE estável (FE-E), definida como alteração da FE <10%. Valores p inferiores a 0,05 foram considerados significativos. Resultados: Dos 377 pacientes com IC grave, 23,3% apresentaram FE-A, 59,5% apresentaram FE-E e 17,2% apresentaram FE-D. Os resultados mostraram ainda 68,2% de insuficiência cardíaca com fração de ejeção reduzida (ICFEr) no grupo FE-A e 64,6% de insuficiência cardíaca com fração de ejeção preservada (ICFEp) no grupo FE-D. Os preditores de FE-A identificados foram faixa etária mais jovem, ausência de diabetes e fração de ejeção do ventrículo esquerdo (FEVE) menor. Já os preditores de FE-D encontrados foram ausência de fibrilação atrial, baixos níveis de ácido úrico e maior FEVE. Em um seguimento mediano de 40 meses, 44,8% dos pacientes foram vítimas de morte por todas as causas. Conclusão: Na IC grave, a ICFEr apresentou maior percentual no grupo FE-A e a ICFEp foi mais comum no grupo FE-D.

Abstract Background: Ejection fraction (EF) has been used in phenotype analyses and to make treatment decisions regarding heart failure (HF). Thus, EF has become a fundamental part of daily clinical practice. Objective: This study aims to investigate the characteristics, predictors, and outcomes associated with EF changes in patients with different types of severe HF. Methods: A total of 626 severe HF patients with New York Heart Association (NYHA) class III-IV were enrolled in this study. The patients were classified into three groups according to EF changes, namely, increased EF (EF-I), defined as an EF increase ≥10%, decreased EF (EF-D), defined as an EF decrease ≥10%, and stable EF (EF-S), defined as an EF change <10%. A p-value lower than 0.05 was considered significant. Results: Out of 377 severe HF patients, 23.3% presented EF-I, 59.5% presented EF-S, and 17.2% presented EF-D. The results further showed 68.2% of heart failure with reduced ejection fraction (HFrEF) in the EF-I group and 64.6% of heart failure with preserved ejection fraction (HFpEF) in the EF-D group. The predictors of EF-I included younger age, absence of diabetes, and lower left ventricular ejection fraction (LVEF). The predictors of EF-D were absence of atrial fibrillation, lower uric acid level, and higher LVEF. Within a median follow-up of 40 months, 44.8% of patients suffered from all-cause death. Conclusion: In severe HF, HFrEF presented the highest percentage in the EF-I group, and HFpEF was most common in the EF-D group.

Incidence and Outcome of Acute Myocardial Infarction in Patients With Aortic Dissection and Risk Factor Control.

Background and Aims: The contradiction of management modality between acute myocardial infarction(AMI) and aortic dissection(AD) may result in clinical catastrophe. Data on risk factors, incidence, and outcome of AD and AMI are limited, and there have been no studies on the long-term outcomes of AMI in patients with AD. So we aimed to investigate long-term outcomes after AMI in patients with AD, and propose a useful diagnostic paradigm. Methods: Consecutively enrolled patients with AD and AMI who were referred to our center from 2010 to 2017. Baseline patient characteristics, risk factors, all medical treatments, echocardiographic parameters, laboratory data, and treatment were recorded. All patients were followed up from the first hospitalization until a first heart event, death, or 17 March, 2018. Results: 0.13% in AMI and 7.49% in AD patients had a concomitant diagnosis of AD and AMI. The average patient age was 53.3 ± 12.1 years and 84.6% were male. The most prevalent vascular risk factors were hypertension (69.2%) and current smoker (64.1%). Of all the 39 patients, 66.7% were managed surgically. Overall in-hospital mortality was 10.3%. The 30-day and 5-year fatality rates were 23.1% and 35.9%, but were higher for female than for male (66.7 vs. 30.3%, log-rank P = 0.045) on 5-year mortality. The overall survival of females was inferior to the males (log-rank P = 0.045). Conclusions: Patients with AMI and AD exhibit high 5-year fatality rates. For these patients, surgical management tends to have lower mortality. Improved management of hypertension and smoking, may reduce future incidence rates.

Application of Machine Learning for Predicting Anastomotic Leakage in Patients with Gastric Adenocarcinoma Who Received Total or Proximal Gastrectomy.

Anastomotic leakage is a life-threatening complication in patients with gastric adenocarcinoma who received total or proximal gastrectomy, and there is still no model accurately predicting anastomotic leakage. In this study, we aim to develop a high-performance machine learning tool to predict anastomotic leakage in patients with gastric adenocarcinoma received total or proximal gastrectomy. A total of 1660 cases of gastric adenocarcinoma patients who received total or proximal gastrectomy in a large academic hospital from 1 January 2010 to 31 December 2019 were investigated, and these patients were randomly divided into training and testing sets at a ratio of 8:2. Four machine learning models, such as logistic regression, random forest, support vector machine, and XGBoost, were employed, and 24 clinical preoperative and intraoperative variables were included to develop the predictive model. Regarding the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy, random forest had a favorable performance with an AUC of 0.89, a sensitivity of 81.8% and specificity of 82.2% in the testing set. Moreover, we built a web app based on random forest model to achieve real-time predictions for guiding surgeons' intraoperative decision making.

Impact of Prior Digestive System Disease on In-Hospital Gastrointestinal Bleeding in Patients with Acute Myocardial Infarction.

OBJECTIVE: Patients presenting with acute myocardial infarction (AMI) with prior digestive system disease are more likely to suffer from gastrointestinal (GI) bleeding than those without these diseases. However, few articles reported how the different conditions of the digestive tract produced different risks of GI bleeding. METHODS: A single-center study on 7464 patients admitted for AMI from December 2010 to June 2019 in the Beijing Chaoyang Heart Center was retrospectively examined. Patients with major GI bleeding (n = 165) were compared with patients without (n = 7299). Univariate and multivariate logistic regression models were constructed to test the association between GI bleeding and prior diseases of the digestive tract, including gastroesophageal reflux disease, chronic gastritis, peptic ulcer, hepatic function damage, diseases of the colon and rectum, and gastroenterological tract tumors. RESULTS: Of the 7464 patients (mean age, 63.4; women, 25.6%; STEMI, 58.6%), 165 (2.2%) experienced major GI bleeding, and 1816 (24.3%) had a history of digestive system disease. The risk of GI bleeding was significantly associated with peptic ulcer (OR = 4.19, 95% CI: 1.86-9.45) and gastroenterological tumor (OR = 2.74, 95% CI: 1.07-7.04), indicated by multivariate logistic regression analysis. CONCLUSION: Preexisting peptic ulcers and gastroenterological tract tumors rather than other digestive system diseases were indicators of gastrointestinal bleeding in patients with AMI who undergo standard antithrombotic treatment during hospitalization.

Serum Inflammatory Factors and Oxidative Stress Factors Are Associated With Increased Risk of Frailty and Cognitive Frailty in Patients With Cerebral Small Vessel Disease.

Objective: To study the correlation between serum inflammatory factors, oxidative stress factors and frailty, and cognitive frailty in patients with cerebral small vessel disease (CSVD). Methods: A total of 281 patients with CSVD were selected from Tianjin Huanhu Hospital and Inner Mongolia People's Hospital from March 2019 to March 2021. CSVD was diagnosed by MRI. The FRAIL scale was used to evaluate the frailty of patients. Patients with CSVD with frailty and MMSE score <27 were considered to have cognitive frailty. Patients with non-cognitive frailty were included in the control group. The Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) were used to evaluate the cognitive function of patients with CSVD. The serum interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase 3 (MMP-3), superoxide dismutase (SOD), and malondialdehyde (MDA) of patients with CSVD were detected. The correlation between blood inflammatory factors and oxidative stress factors with the frailty and cognitive frailty patients of CSVD were analyzed. Univariate and multivariate logistic regression were used to analyze the correlation between cognitive frailty and CSVD. Results: Among the patients with CSVD selected in this study, female patients and older patients had a higher proportion of frailty (p < 0.001). In the Frail group, MoCA score and MMSE score were significantly lower than in the Pre-Frail and Robust groups, Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) scores were significantly higher than the Pre-Frail and Robust groups, and the differences were statistically significant (p < 0.05). Serum CRP, IL-6, TNF-α, MMP-3, and MDA levels in the Frail group were higher, but SOD levels were lower. The levels of serum CRP, IL-6, TNF-α, MMP-3, and MDA in patients with CSVD in the Cognitive Frailty group were significantly higher than those of the Control group, while the levels of SOD were significantly lower than those of the Control group, and the differences were significant (p < 0.001). The results of univariate and multivariate logistic regression analysis showed that CRP, TNF-α, MMP-3, and MDA levels were associated with cognitive frailty in patients with CSVD (p < 0.05). Conclusion: The increase of serum CRP, TNF-α, MMP-3, and MDA levels are significantly related to the increased risk of frailty and cognitive frailty in patients with CSVD.

Differentiated cancer cell-originated lactate promotes the self-renewal of cancer stem cells in patient-derived colorectal cancer organoids.

Tumors harbor diverse compartments of cells with distinct metabolic properties and phenotypes, but the mechanism by which metabolic commensalism among distinct subsets of cancer cells affects tumor progression remains unclear. Colorectal cancer (CRC) has been reported to consist of cancer stem cells (CSCs) and differentiated cancer cells (non-CSCs). In the present study, organoid models were employed to show that CSCs and non-CSCs in CRC were characterized by distinct metabolic phenotypes. Treatment with either non-CSC-derived conditioned medium or exogenous lactate enhanced organoid-forming and tumor-initiating capacity of CSCs. In tumor regeneration assays with co-implanted CSCs and non-CSCs, the tumor-initiating activity was reduced when either monocarboxylate transporter (MCT)4 in non-CSCs or MCT1 in CSCs was silenced or inhibited. Mechanistically, oxiadative phosphorylation-derived reactive oxygen species in CSCs activated AKT-Wnt/ß-catenin signaling, which could be induced by lactate from non-CSCs. Overall, these results suggest that CSCs and non-CSCs possess distinct metabolic profiles and, unexpectedly, non-CSC-originated lactate promotes self-renewal of CSCs and thus contributes to CRC progression. Our findings establish a rationale for developing novel therapies targeting the metabolic commensalism between different cell populations in CRC.